ArticleArchives of biochemistry and biophysics2016
Enhanced troponin I binding explains the functional changes produced by the hypertrophic cardiomyopathy mutation A8V of cardiac troponin C.
Article in Archives of biochemistry and biophysics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 19 citations in OpenAlex.
- Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C.International journal of molecular sciences · 2023Review
- The effect of MgThe FEBS journal · 2022Article
- Cardiomyocyte Dysfunction in Inherited Cardiomyopathies.International journal of molecular sciences · 2021Review
- De Novo Missense Mutations inInternational journal of molecular sciences · 2021Article
- Potential impacts of the cardiac troponin I mobile domain on myofilament activation and relaxation.Journal of molecular and cellular cardiology · 2021Article
- A comprehensive guide to genetic variants and post-translational modifications of cardiac troponin C.Journal of muscle research and cell motility · 2021Article
- Eliminating the First Inactive State and Stabilizing the Active State of the Cardiac Regulatory System Alters Behavior in Solution and in Ordered Systems.Biochemistry · 2020Article
- Basic residues within the cardiac troponin T C terminus are required for full inhibition of muscle contraction and limit activation by calcium.The Journal of biological chemistry · 2019Article
- Structural and functional impact of troponin C-mediated CaJournal of molecular and cellular cardiology · 2018Article
- Changes in the dynamics of the cardiac troponin C molecule explain the effects of CaThe Journal of biological chemistry · 2017Article
- Troponin C Mutations Partially Stabilize the Active State of Regulated Actin and Fully Stabilize the Active State When Paired with Δ14 TnT.Biochemistry · 2017Article
- Hypertrophic Cardiomyopathy Cardiac Troponin C Mutations Differentially Affect Slow Skeletal and Cardiac Muscle Regulation.Frontiers in physiology · 2017Article
- Myofilament modulation of contraction.Archives of biochemistry and biophysics · 2016Article
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
- Modeling CaFrontiers in physiology · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Higher affinity for TnI explains how troponin C (TnC) carrying a causative hypertrophic cardiomyopathy mutation, TnC(A8V), sensitizes muscle cells to Ca(2+). Muscle fibers reconstituted with TnC(A8V) require ∼2.3-fold less [Ca(2+)] to achieve 50% maximum-tension compared to fibers reconstituted with wild-type TnC (TnC(WT)). Binding measurements rule out a significant change in N-terminus Ca(2+)-affinity of isolated TnC(A8V), and TnC(A8V) binds the switch-peptide of troponin-I (TnI(sp)) ∼1.6-fold more strongly than TnC(WT); thus we model the TnC-TnI(sp) interaction as competing with the TnI-actin interaction. Tension data are well-fit by a model constrained to conditions in which the affinity of TnC(A8V) for TnI(sp) is 1.5-1.7-fold higher than that of TnC(WT) at all [Ca(2+)]. Mean ATPase rates of reconstituted cardiac myofibrils is greater for TnC(A8V) than TnC(WT) at all [Ca(2+)], with statistically significant differences in the means at higher [Ca(2+)]. To probe TnC-TnI interaction in low Ca(2+), displacement of bis-ANS from TnI was monitored as a function of TnC. Whereas Ca(2+)-TnC(WT) displaces significantly more bis-ANS than Mg(2+)-TnC(WT), Ca(2+)-TnC(A8V) displaces probe equivalently to Mg(2+)-TnC(A8V) and Ca(2+)-TnC(WT), consistent with stronger Ca(2+)-independent TnC(A8V)-TnI(sp). A Matlab program for computing theoretical activation is reported. Our work suggests that contractility is constantly above normal in hearts made hypertrophic by TnC(A8V).
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